Dynamic nuclear polarisation NMR of nanosized zirconium phosphate polymer fillers

International audience; Surface functionalisation with organic modifiers of multi-layered zirconium phosphate (ZrP) nanoparticles used as polymer fillers can be directly probed by dynamic nuclear polarisation NMR, which provides unambiguous evidence of the presence of P-O-C chemical bonds at the surface of the ZrP layers, thereby confirming successful functionalisation

Développement de nouveaux dinitroxydes comme agents de polarisation efficaces pour la Polarisation Dynamique Nucléaire associée à la RMN du solide

Depuis sa découverte, la spectroscopie de Résonance Magnétique Nucléaire (RMN) a permis de grandes avancées scientifiques dans de nombreux domaines allant de la physique à la médecine. L'inconvénient majeur de la RMN est sa faible sensibilité intrinsèque, due à la très faible polarisation des spins nucléaires. Au cours de ces 20 dernières années, la Polarisation Dynamique Nucléaire (PDN) s'est développée comme technique très prometteuse permettant d'augmenter la polarisation de spin nucléaire, et l'intensité des signaux en RMN liquide ou solide de plusieurs ordres de grandeur. Dans les mêmes conditions expérimentales, la polarisation de spin de l'électron est beaucoup plus grande que la polarisation de spin nucléaire et la PDN permet le transfert de cette forte polarisation à partir d'un agent de polarisation paramagnétique (habituellement un radical libre organique) vers les noyaux avoisinants. L'augmentation de l'intensité du signal RMN (I) est caractérisé par un facteur d'exaltation ε=I(μw ON)/I(μw OFF).L'objectif principal de cette thèse est la synthèse d'agents de polarisation, de type dinitroxyde, solubles dans l'eau et très efficaces pour des expériences de MAS ssNMR/PDN. Nous avons préparé une large série de dérivés du bTurea solubles dans l'eau et leurs performances PDN ont été évaluées à différent champs magnétiques. En remplaçant les groupements méthyl des fonctions TEMPO par des cycles pyranyl, ainsi qu'en introduisant des chaînes PEG sur le linker urée, AMUPol (ε=247) et PyPolPEG2OH (ε=303) ont entre autres été obtenus. Ce sont actuellement les agents de polarisation les plus efficaces pour des expériences de MAS ssNMR/PDN en milieux aqueux.Nowadays, Nuclear Magnetic Resonance (NMR) spectroscopy has become a very powerful technique that can be used to address a wide range of problems, ranging from physics to medicine. The major limitation of NMR is its intrinsic low sensitivity, resulting from the very small nuclear spin polarizations observed even at high magnetic fields. During the last two decades, Dynamic Nuclear Polarization (DNP) has emerged as a very promising approach to enhance NMR signal intensities of solids and liquids by several orders of magnitude. All things being equal, electron spin polarization is much higher than nuclear spin polarization and DNP exploits the microwave-driven transfer of polarization from a paramagnetic polarizing agent (usually an added exogenous organic free radical) to the surrounding nuclei. The enhancement of NMR signal intensities (I) is characterized by the enhancement factor ε=I(μw ON)/I(μw OFF). The main objective of this PhD thesis was the development of new water-soluble dinitroxides, highly efficient polarizing agents for MAS solid-state NMR/DNP applications. We have designed and prepared a large series of water-soluble bTurea (TEMPO-N(H)-C(O)-(H)N-TEMPO), derivatives, and their DNP performance was tested at different magnetic fields (mainly 9.4 T). Replacing the methyl groups of TEMPO moieties with pyranyl rings, and introducing PEG chains on the urea linker we obtained, among others, two derivatives, AMUPol (ε = 247) and PyPolPEG2OH (ε = 303) which are currently the most efficient water-soluble polarizing agents for MAS ssNMR/DNP experiments for aqueous media

A Multi‐Component Reaction towards the Development of Highly Modular Hydrogelators

Herein we report a multi‐component reaction approach for the development of a new class of hydrogelators based on the OxoTriphenylHexanOate (OTHO) backbone. A focused library of OTHOs has been synthesized and their hydrogelation features evaluated. The two most potent hydrogelators were studied by rheology revealing different stiffness, appearances and thixotropic behavior of the gels. The new gelators showcase the versatility of the OTHO backbone as a platform for the design of functionalized hydrogels with tunable gel properties.peerReviewe

Highly Efficient, Water-Soluble Polarizing Agents for Dynamic Nuclear Polarization at High Frequency

International audienceWell polarized: Two new polarizing agents PyPol and AMUPol soluble in glycerol/water mixtures are used for dynamic nuclear polarization (DNP) NMR spectroscopy. The enhancement factors (ε) are about 3.5 to 4 times larger than for the established agent TOTAPOL at 263 and 395 GHz. For AMUPol, the temperature dependence of ε allows DNP experiments to be performed at temperatures significantly higher than for typical high-field DNP NMR experiments

Biomolecular DNP-Supported NMR Spectroscopy using Site-Directed Spin Labeling

International audienceDynamic nuclear polarization (DNP) has beenshown to greatly enhance spectroscopic sensitivity, creatingnovel opportunities for NMR studies on complex and largemolecular assemblies in life and material sciences. In suchapplications, however, site-specificity and spectroscopic resolutionbecome critical factors that are usually difficult to controlby current DNP-based approaches. We have examinedin detail the effect of directly attaching mono- or biradicalsto induce local paramagnetic relaxation effects and, at thesame time, to produce sizable DNP enhancements. Usinga membrane-embedded ion channel as an example, wevaried the degree of paramagnetic labeling and the locationof the DNP probes. Our results show that the creation oflocal spin clusters can generate sizable DNP enhancementswhile preserving the intrinsic benefits of paramagnetic relaxationenhancement (PRE)-based NMR approaches. DNPusing chemical labeling may hence provide an attractiveroute to introduce molecular specificity into DNP studies inlife science applications and beyond

Rational design of dinitroxide biradicals for efficient cross-effect dynamic nuclear polarization

A series of 37 dinitroxide biradicals have been prepared and their performance studied as polarizing agents in cross-effect DNP NMR experiments at 9.4 T and 100 K in 1,1,2,2-tetrachloroethane (TCE). We observe that in this regime the DNP performance is strongly correlated with the substituents on the polarizing agents, and electron and nuclear spin relaxation times, with longer relaxation times leading to better enhancements. We also observe that deuteration of the radicals generally leads to better DNP enhancement but with longer build-up time. One of the new radicals introduced here provides the best performance obtained so far under these conditions.ISSN:2041-6520ISSN:2041-653

Tailoring of Polarizing Agents in the bTurea Series for Cross-Effect Dynamic Nuclear Polarization in Aqueous Media

International audienceA series of 18 nitroxide biradicals derived from bTurea has been prepared, and their enhancement factors ɛ (1H) in cross-effect dynamic nuclear polarization (CE DNP) NMR experiments at 9.4 and 14.1 T and 100 K in a DNP-optimized glycerol/water matrix (“DNP juice”) have been studied. We observe that ɛ (1H) is strongly correlated with the substituents on the polarizing agents, and its trend is discussed in terms of different molecular parameters: solubility, average e–e distance, relative orientation of the nitroxide moieties, and electron spin relaxation times. We show that too short an e–e distance or too long a T1e can dramatically limit ɛ (1H). Our study also shows that the molecular structure of AMUPol is not optimal and its ɛ (1H) could be further improved through stronger interaction with the glassy matrix and a better orientation of the TEMPO moieties. A new AMUPol derivative introduced here provides a better ɛ (1H) than AMUPol itself (by a factor of ca. 1.2)

APP, PSEN1, and PSEN2 mutations in early-onset Alzheimer disease: A genetic screening study of familial and sporadic cases

International audienceBackgroundAmyloid protein precursor (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2) mutations cause autosomal dominant forms of early-onset Alzheimer disease (AD-EOAD). Although these genes were identified in the 1990s, variant classification remains a challenge, highlighting the need to colligate mutations from large series.Methods and findingsWe report here a novel update (2012–2016) of the genetic screening of the large AD-EOAD series ascertained across 28 French hospitals from 1993 onwards, bringing the total number of families with identified mutations to n = 170. Families were included when at least two first-degree relatives suffered from early-onset Alzheimer disease (EOAD) with an age of onset (AOO) ≤65 y in two generations. Furthermore, we also screened 129 sporadic cases of Alzheimer disease with an AOO below age 51 (44% males, mean AOO = 45 ± 2 y). APP, PSEN1, or PSEN2 mutations were identified in 53 novel AD-EOAD families. Of the 129 sporadic cases screened, 17 carried a PSEN1 mutation and 1 carried an APP duplication (13%). Parental DNA was available for 10 sporadic mutation carriers, allowing us to show that the mutation had occurred de novo in each case. Thirteen mutations (12 in PSEN1 and 1 in PSEN2) identified either in familial or in sporadic cases were previously unreported. Of the 53 mutation carriers with available cerebrospinal fluid (CSF) biomarkers, 46 (87%) had all three CSF biomarkers—total tau protein (Tau), phospho-tau protein (P-Tau), and amyloid β (Aβ)42—in abnormal ranges. No mutation carrier had the three biomarkers in normal ranges. One limitation of this study is the absence of functional assessment of the possibly and probably pathogenic variants, which should help their classification.ConclusionsOur findings suggest that a nonnegligible fraction of PSEN1 mutations occurs de novo, which is of high importance for genetic counseling, as PSEN1 mutational screening is currently performed in familial cases only. Among the 90 distinct mutations found in the whole sample of families and isolated cases, definite pathogenicity is currently established for only 77%, emphasizing the need to pursue the effort to classify variants

Dendritic polarizing agents for DNP SENS

We acknowledge Patrick Wolf for providing the Sn zeolite sample. We thank Dr Rene Verel for the technical support in the LAC NMR facility at ETHZ and fruitful discussions. We thank Lenaic Leroux for his technical support for the experiments conducted on the 400 MHz DNP spectrometer in Lyon.International audienceDynamic Nuclear Polarization Surface Enhanced NMR Spectroscopy (DNP SENS) is an effective method to significantly improve solid-state NMR investigation of solid surfaces. The presence of unpaired electrons (polarizing agents) is crucial for DNP, but it has drawbacks such as leading to faster nuclear spin relaxation, or even reaction with the substrate under investigation. The latter can be a particular problem for heterogeneous catalysts. Here, we present a series of carbosilane-based dendritic polarizing agents, in which the bulky dendrimer can reduce the interaction between the solid surface and the free radical. We thereby preserve long nuclear T'2 of the surface species, and even successfully enhance a reactive heterogeneous metathesis catalyst